Longitudinal and structural neuroimaging studies show that patients with schizophrenia that converted to psychosis were found to have progressive gray matter loss in the cortex. Gray matter loss was also associated with functional decline. While the underlying mechanisms of gray matter loss remain uncertain, evidence of improved outcomes suggests neuroprotection, the maintenance of the functional integrity of the brain in response to neurobiological stress, in schizophrenia is possible. In order to protect against gray matter loss and slow functional decline following the onset of psychosis, new data suggests that an appropriate antipsychotic chosen at first episode can modify the rate of structural deterioration, which can lead to improved outcome.